crossing96/oncoscreening huggingface dataset:
Multiparametric MRI for local staging in patients with suspected muscle-invasive bladder cancer: study protocol for a multicentre, non-inferiority randomised controlled trial (the BladParadigm study).	INTRODUCTION: Muscle-invasive bladder cancer (MIBC) is an aggressive type of cancer. About 50% of patients will die from the disease within 5 years despite radical treatment. This implies that in many patients, the disease has already spread at the time of radical treatment, even though imaging shows no signs of metastasis. We hypothesise that the standard local staging method, transurethral resection of the bladder tumour (TURBT), is partly responsible for tumour cell spread. Furthermore, TURBT (and re-TURBT in many patients) contributes to a significant delay to definitive therapy. The aim of this randomised study is to determine whether multiparametric MRI (mpMRI) of the bladder, in combination with a single outpatient bladder tumour biopsy for histological confirmation, is a safer, faster, less costly and, therefore, more cost-effective diagnostic pathway than TURBT to detect or rule out MIBC. METHODS AND ANALYSIS: BladParadigm is a two-arm multicentre randomised controlled trial (RCT) conducted in the Netherlands. Over a 3-year period, patients with clinically suspected MIBC without evidence of metastases will be recruited and randomised 1:1 to either TURBT or 3-Tesla mpMRI with same-day outpatient bladder biopsy. The Vesical Imaging Reporting and Data System (VI-RADS) will be used to standardise mpMRI reporting. Patients will undergo definitive treatment based on the results of the TURBT or mpMRI. The study is powered to demonstrate that the mpMRI-based strategy is at least non-inferior to standard TURBT in patients treated with radical cystectomy alone, assuming a relative hazard of 0.55. The required sample size is 360 patients (180 TURBT, 180 mpMRI). The primary outcome is 2-year progression-free survival. Progression will be assessed by imaging, according to the current standard of care. Secondary outcome measures are time to definitive treatment, quality of life (EuroQol 5D-5L), healthcare costs and cost-effectiveness. ETHICS AND DISSEMINATION: This study has received ethical approval from the Medical Ethical Committee Oost-Nederland (NL83685.091.23). All participants will provide written informed consent prior to inclusion. Findings of this study will be disseminated through peer-reviewed, open-access publications, presentations at scientific conferences and stakeholder briefings. TRIAL REGISTRATION NUMBER: NCT05779631.	bladder
Do urinary bladder smooth muscle neoplasms show morphologic and immunophenotypic features of their uterine fumarate hydratase-deficient counterparts?	"While the morphologic and immunophenotypic features of smooth muscle neoplasms of the uterus and skin have been well-described in relationship to fumarate hydratase (FH) deficiency (FHD), a potential association of urinary bladder smooth muscle tumors with FH tumor predisposition syndrome (FHTPS) has not been previously investigated. Given an index urinary bladder leiomyoma which showed some of the purported morphologic features seen in uterine FHD leiomyomas, we performed a multi-institutional search for bladder smooth muscle tumors to further evaluate a putative FHTPS association. Cases were re-reviewed for the presence of the following well-described FHD-associated cytomorphologic features: macronucleoli (""cherry red"") surrounded by halo, isolated nuclear pleomorphism (""symplastic"" nuclei), cytoplasmic eosinophilic globules, staghorn vasculature, alveolar-pattern edema, and chain-like distribution of smooth muscle fibers. Tumors with available material underwent whole-slide staining for FH and 2SC immunohistochemistry. A total of 40 bladder smooth muscle tumors (35 leiomyomas, 5 leiomyosarcomas) were collected from patients (33 females, 17 males) of ages 30-86 years (mean=56.3 years). Among leiomyomas, cytoplasmic eosinophilic globules were seen most frequently (31%), followed by CMV-like macronucleoli (17%), staghorn-type vasculature (11%), ""symplastic"" nuclei (9%), and alveolar-pattern edema (6%). Among the leiomyosarcomas, cytoplasmic eosinophilic globules or CMV-like macronucleoli were infrequently seen (20%), while staghorn-type vasculature was seen in 60% and ""symplastic"" nuclei were seen in all (100%) tumors. No cases exhibited chain-like muscle fibers. Of the stained tumors, all (100%) showed retained FH expression and negative 2SC immunoreactivity. Three female patients with bladder leiomyomas had a prior history of uterine leiomyomas all lacking FHD histology. Although a subset of bladder smooth muscle tumors show overlapping morphologic features with uterine FHD leiomyomas, they do not appear to harbor FHD or an association with FHTPS, although the findings warrant confirmation in future studies, perhaps inclusion of FH and/or 2SC immunohistochemistry."	bladder
Hyperthermic intravesical chemotherapy for Bacillus Calmette-Guérin-unresponsive nonmuscle-invasive bladder cancer.	PURPOSE OF REVIEW: Hyperthermic intravesical chemotherapy (HIVEC) and other device-assisted platforms are emerging bladder-sparing options after Bacillus Calmette-Guérin (BCG) failure in nonmuscle-invasive bladder cancer (NMIBC). This review integrates recent mechanistic, clinical and economic evidence to clarify their therapeutic position. RECENT FINDINGS: Prospective and real-world series in BCG-unresponsive disease report complete response rates of 40-60% for carcinoma in situ and 35-70% 12-24-month high-grade recurrence-free survival for papillary tumors. Radiofrequency-induced thermo-chemotherapy, recirculant chemohyperthermia and electromotive drug administration achieve comparable efficacy. Toxicity is usually grade 1-2 urinary urgency, frequency or dysuria, with serious events in fewer than 10% of patients. Health-economic modelling suggests HIVEC becomes cost-effective once high-grade recurrence-free survival exceeds 30% at 12 months. SUMMARY: Device-assisted hyperthermic chemotherapy combines biological plausibility, acceptable safety and favorable cost, positioning it as a potential option between BCG failure and radical cystectomy. Ongoing phase III trials will determine long-term oncological control, refine patient selection and optimize sequencing with systemic and intravesical agents.	bladder
Hypoxia-induced PYCR1 regulates glycolysis and histone lactylation to promote bladder cancer progression and metastasis via SLC6A14/Glutamine metabolism.	Hypoxia-induced Pyrroline-5-Carboxylate Reductase 1 (PYCR1) is implicated in bladder cancer (BC), but its specific role remains elusive. This study investigated how PYCR1 promotes BC progression through glycolysis, histone H3 Lysine 18 Lactylation (H3K18la), and Solute Carrier Family 6 Member 14 (SLC6A14)-driven glutamine catabolism. Here, BC cell lines were cultured under hypoxia to evaluate changes in PYCR1 expression, glycolysis, and lactate production. The xenograft and metastasis models in nude mice were used to validate the role of the PYCR1/H3K18la/SLC6A14 axis in BC progression. GEPIA Bioinformatics database data showed that PYCR1 was upregulated in BC and was associated with poor prognosis. The PYCR1 positive expression rate in BC tissues was increased. Hypoxia induced PYCR1 expression in BC cells, enhancing glycolysis and lactate production, which increased H3K18la levels. Upregulated SLC6A14 expression promoted glutamine catabolism and enhanced BC cell proliferation, migration, and invasion. PYCR1 knockdown inhibited H3K18la levels, SLC6A14 expression, and BC cell aggressiveness; SLC6A14 overexpression reversed these effects. In vivo experiments confirmed that the PYCR1/H3K18la/SLC6A14 axis is critical for hypoxia-driven BC growth and metastasis. In summary, Hypoxia-induced PYCR1 enhances glycolysis, leading to increased lactate production and elevated H3K18la levels, which upregulates SLC6A14 transcription and glutamine catabolism, thereby promoting BC growth and metastasis.	bladder
Association of miRNA-17-92 Cluster with Muscle Invasion in Bladder Cancer.	Bladder cancer (BC) is the most frequent cancer of the urinary system and one of the most common malignancies in the world. In the last decade, many studies have been conducted to better understand the pathophysiological mechanisms of BC to find innovative markers for disease monitoring and treatment. In this study, we aim to identify miRNAs whose expression is associated with specific tumoral characteristics and risks of disease progression. Forty-one BC patients were enrolled in this study. The expression of 84 miRNAs was evaluated by qRT-PCR analysis on tumoral and peritumoral tissues. The results highlighted the association of the miRNA-17-92 cluster with BC, with miR-17-5p, miR-18a-5p, miR-19a-3p, and miR-20a-5p (members of this cluster) being upregulated in the tumoral tissue and correlated with muscle invasion and tumor grading. Taken together, our study identified a panel of 26 dysregulated miRNAs in BC, some of which may be associated with aggressiveness and the risk of progression of this malignancy.	bladder
Nuclear Receptors in Bladder Cancer: Insights into miRNA-Mediated Regulation and Potential Therapeutic Implications.	Nuclear receptors (NRs) are ligand-activated transcription factors that regulate gene expression and are involved in diverse physiological and pathological processes, including carcinogenesis. In bladder cancer (BCa), dysregulation of NR signaling pathways has been linked to tumor initiation, progression, therapy resistance, and immune evasion. Recent evidence highlights the intricate crosstalk between NRs and microRNAs (miRNAs), which are small non-coding RNAs that posttranscriptionally modulate gene expression. This review provides an integrated overview of the molecular interactions between key NRs and miRNAs in BCa. We investigated how miRNAs regulate NR expression and function and, conversely, how NRs influence miRNA biogenesis, thereby forming regulatory feedback loops that shape tumor behavior. Specific miRNA-NR interactions affecting epithelial-to-mesenchymal transition, metabolic reprogramming, angiogenesis, and chemoresistance are discussed in detail. Additionally, we highlight therapeutic strategies targeting NR-miRNA networks, including selective NR modulators, miRNA mimics and inhibitors, as well as RNA-based combinatorial approaches focusing on their utility as diagnostic biomarkers and personalized treatment targets. Understanding the molecular complexity of NR-miRNA regulation in BCa may open new avenues for improving therapeutic outcomes and advancing precision oncology in urological cancers.	bladder
A Double-Humanized Murine Model in Bladder Cancer: A Novel Preclinical Model for Cancer Immunology Research.	BACKGROUND: Bladder cancer (BC) ranks as the 10th leading cause of cancer-related deaths in the United States. Despite significant advancements in managing BC, including antibody-drug conjugates and immune checkpoint blockers, a significant percentage of patients fail these treatments. This underscores the pressing need to develop methods for identifying novel therapeutic targets, predicting therapy responses, and optimizing personalized treatment strategies for patients. Patient-derived xenograft (PDX) models have the potential to address these challenges. However, these models suffer from limitations, including a consistent rate of tumor acceptance, extended time for tumor growth, and the absence of the donor's immune system. METHODS: This study aimed to address these challenges through a comprehensive comparison of different PDX implantation methods, culminating in the establishment of a PDX cell line for utilization in in vivo BC preclinical models. Flow cytometry analysis and total RNA sequencing were used for comparative analysis of original tumor tissue, PDX tumor, and PDX257S cell line. RESULTS: Tumor tissue processing techniques were optimized to enhance the rate of PDX tumor acceptance and shorten the time to tumor development. Furthermore, a PDX cell line, PDX257S, was successfully established and confirmed to exhibit more aggressive and tumorigenic characteristics compared to the original donor tumor tissue. The PDX257S cell line demonstrated faster tumor growth, higher expression of human epithelial cell adhesion molecule, increased mutation burden in BC-associated genes, and significant alterations in BC-related gene expression, compared to the original tumor. The PDX257S cell line was also used to establish a double humanized BC murine model that minimized graft-versus-host disease and is a potential platform for testing novel immune therapeutics. CONCLUSIONS: In summary, this study offers an optimized protocol for the consistent establishment of BC PDX tumors. Furthermore, it has also established a novel double-humanized model, demonstrating the potential for drug screening and clinical prognosis in the context of BC treatment.	bladder
Fusobacterium nucleatum promotes bladder cancer progression and immune escape by activating the IL22/STAT3/PD-L1 signaling cascade.	OBJECTIVE: This study investigates the mechanism by which Fusobacterium nucleatum (Fn) promotes bladder cancer (BC) progression and immune escape through the interleukin 22 (IL22)/signal transducer and activator of transcription 3 (STAT3)/programmed death-ligand 1 (PD-L1) cascade signaling. METHODS: Fecal samples from BC patients (n = 73) and healthy controls (n = 39) were analyzed for Fn abundance using qRT-PCR. IL-22, p-STAT3, STAT3, and PD-L1 levels were determined by qRT-PCR and western blot. The in vitro cultured human BC cell line (T24) were co-cultured with Fn, followed by CCK-8, colony formation, and Transwell assays to assess cell viability, proliferation, and invasion and migration, respectively. A co-culture system of T24 and CD8-positive T lymphocytes (CD8(+) T) cells was established. Immune responses were assessed by determining tumor necrosis factor alpha (TNF-α), interferon gamma (INF-γ), granzyme B (GZMB), and pore-forming protein (Perforin) levels in supernatants. In vivo studies using a BC mouse model examined tumor progression and immune markers through flow cytometry, focusing on CD8(+) T cells and regulatory T cell (Treg) populations. Immunohistochemical assay was conducted to measure ki67 levels in tumor tissues. RESULTS: Fn levels were significantly elevated in BC patients' feces. Fn treatment enhanced cancer cell viability, proliferation, invasion, and migration. Fn activated the IL22/STAT3/PD-L1 pathway and showed positive correlations with these markers in BC tissues. In the co-culture system, Fn reduced CD8(+) T cell function and increased Treg proportions in tumor tissues. The in vivo experiments confirmed that Fn promoted IL22/STAT3/PD-L1 expression, altered immune cell ratios, and increased ki67 expression levels. CONCLUSION: Fn promotes the IL22/STAT3/PD-L1 cascade signaling, thereby facilitating in vivo progression and immune evasion of BC.	bladder
Integrated photoelectrochemical/photothermal dual-mode biosensor with simultaneous dual-signal output for detection of bladder cancer cells HT-1376.	Here, a photoelectrochemical (PEC)/photothermal (PT) dual-mode biosensing platform with simultaneous output of response signals was developed for sensitive and accurate detection of bladder tumor cells HT-1376. The system utilized an infrared laser as a shared light source, with photocurrent and temperature measurements acquired through parallel PEC and PT detection channels. The HT-1376-specific aptamer (Apt) was covalently immobilized on aminated indium‑tin oxide (ITO) electrode via glutaraldehyde crosslinking between surface amino groups and amine-modified aptamer terminals, enabling selective target capture. Following aptamer-HT-1376 recognition, the dual-mode tags CuO@NPC functionalized with aptamer (CuO@NPC-Apt) were assembled on the electrode surface, triggering simultaneous PEC and PT signal responses. Under optimized conditions, linear detection ranges of 5-10(5) cells/mL (PEC mode) and 10-10(5) cells/mL (PT mode) were achieved, with limits of detection (LOD) of 3 cells/mL (PEC) and 5 cells/mL (PT). The platform exhibited excellent signal stability, repeatability and selectivity. This dual-mode strategy provides a reliable analytical method for HT-1376 quantification, demonstrating potential for clinical cancer diagnostics.	bladder
Outcome of atypical urothelial cells (AUC) in patients without prior history of urothelial carcinoma.	"INTRODUCTION: An ""atypical"" diagnosis is subjective in any cytologic specimen, and the interpretation is often problematic. To mitigate this issue, The Paris System for Reporting Urinary Cytology was released in 2016. Its goal was to standardize the criteria for urine cytology specimens. Atypical urothelial cells (AUC) can be a difficult diagnosis for clinicians to utilize, as it does not give a definitive answer as to whether a patient has a urothelial malignancy or not. However, a diagnosis of AUC is an acceptable option for a urine specimen that has characteristics that are clearly abnormal but fall short of malignancy. MATERIALS AND METHODS: Voided urine specimens signed out as AUC in 2019 and 2020 from patients without a history of urothelial carcinoma were identified using the laboratory information system. Patient history, clinical history, and follow-up through April of 2024 were recorded. Selected cases were reviewed microscopically for the AUC diagnosis on the voided urine specimen. RESULTS: Of 151 cases identified, 50 (33.0%) cases included biopsy follow-up, and one case had follow-up of a ureteral brushing. Of those 51 cases, 33 (64.7%) cases had a positive follow-up, 12 (23.5%) cases had a negative follow-up, and 6 (11.8%) cases had a follow-up that showed a nonurothelial malignancy. CONCLUSIONS: Previous similar studies have evaluated the outcome of AUC diagnoses, but it is common for those patients to have had a prior history of urothelial carcinoma. In this study, the diagnosis of AUC correlates to an eventual diagnosis of malignancy in 63.0% of cases without a known history of urothelial carcinoma. Based upon these results and previous studies, AUC appears to be a beneficial diagnosis for the patient but may lead to variable outcomes in patient follow-up."	bladder
Habitat-based radiomic model for predicting muscle invasion in bladder cancer: A multi-center study using enhanced-CT and machine learning.	BACKGROUND: Accurate assessment of muscle invasion in bladder cancer is crucial for guiding treatment and prognosis. Habitat-based radiomics, which accounts for tumor heterogeneity, may enhance evaluation of tumor status and outcomes. PURPOSE: This research primarily investigates the efficacy of a novel habitat-based radiomic model in predicting muscle invasion in bladder cancer. METHODS: We retrospectively analyzed 325 bladder cancer patients from two institutions (July 2018-July 2023). Patients were divided into a training cohort (231 cases, Institution 1) and an external test cohort (94 cases, Institution 2). CT images were standardized, and areas of interest (AOIs) were delineated. Nineteen texture features were extracted from each AOI, and K-means clustering identified intratumoral habitats. Radiomic features from each habitat were extracted using PyRadiomics and used to build a habitat model with the ExtraTree algorithm. For comparison, we also developed uniphase, multiphase, and clinical models. Model performance was evaluated by sensitivity, specificity, accuracy, and area under the ROC curve (AUC). The Delong test compared diagnostic performance between models. RESULTS: Three distinct habitats were identified within bladder tumors. The habitat model achieved an AUC of 0.947 (95% CI: 0.911-0.982) in the training cohort and 0.825 (95% CI: 0.704-0.946) in the external test cohort. In the training cohort, the habitat model outperformed the uniphase (p = 0.003), multiphase (p = 0.036), and clinical models (p = 0.049). The combined habitat and clinical model showed superior diagnostic performance compared to uniphase (p = 0.019) and multiphase clinical (p = 0.069) fusion models. The radiomics signature integrating habitat and multiphase features reliably predicted muscle invasion across the entire cohort (AUC = 0.922, 95% CI: 0.883-0.960). CONCLUSIONS: Habitat-based radiomic features combined with machine learning enable accurate preoperative prediction of muscle invasion in bladder cancer using CT images.	bladder
Long live the kidney despite every threats: a case report.	Kidneys are functionally affected by the diseases of other organs. Here, we present an elderly predialysis patient with a functioning kidney for 10 years of nephrological follow-up despite many comorbidities. A 75-year-old male patient with a medical history of hypertension for 15 years and 60 pack years of cigarette smoking, was diagnosed as muscle invasive bladder cancer (MIBC) and synchronous centrally located clear cell renal cell carcinoma (ccRCC) in the left kidney. At admission, the patient had an Estimated Glomerular Filtration Rate (eGFR) (CKD-EPI-cre) of 54mL/min/1.73m(2), after left nephrectomy eGFR of the patient decreased to 35 mL/min/1.73m(2). After ten years of follow-up, the patient's right kidney had been functional with a eGFR of 24 mL/min/1.73m(2) despite radical cystectomy with urinary diversion, radical nephrectomy, heavy smoking, [cardiorenal syndrome, chronic obstructive pulmonary disease, and hypertension. It is well known that comorbidities such as hypertension, smoking, cancers, infections, pulmonary and heart diseases contribute to irreversible kidney damage and are additive to decreasing kidney function. Appropriate and early diagnosis and treatment of these comorbidities permit healthy aging of the kidneys without the need for dialysis.	bladder
Intravesical delivery of mucoadhesive and tumor-selective-penetrating nanozymes for enhancing the PDT of bladder cancer.	Intravesical photodynamic therapy (PDT) emerges as a promising modality for bladder cancer treatment, yet its efficacy is often curtailed by weak muco-adhesion, poor muco-penetration, low tumor-targeting and intra-tumoral oxygen scarcity. In this work, we introduce a drug delivery system leveraging cerium oxide (CeO(2)) nanozymes as the core, polyarginine peptides R11 as the tumor-targeting ligands, and indocyanine green (ICG) as the photosensitizers, with the latter two components assembled on the particle surface. Intravesical ICG@R11-CeO(2) nanoparticles displayed enhanced mucoadhesive, mucus-penetrating and tumor-targeting properties, and effectively mitigated the hypoxia threat in the tumor microenvironment to improve the PDT sensitivity. Remarkably, the intravesical PDT via ICG@R11-CeO(2) nanoparticles achieved complete tumor inhibition in orthotopic bladder cancer models, offering strong evidence on its clinical translational potential.	bladder
Letter to editor: SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer.	"We are writing to commend the recent article by Zhuang et al. titled ""SIGMAR1 screened by a GPCR-related classifier regulates endoplasmic reticulum stress in bladder cancer,"" published in the Journal of Translational Medicine. This is a highly innovative and clinically significant article that seamlessly integrates bioinformatics and functional analysis to identify SIGMAR1 as a key regulator of endoplasmic reticulum (ER) stress in bladder cancer (BC). Additionally, it establishes a GPCR-tumor microenvironment (TME) classification system combining 15 GPCRs and five immune cell types, offering a novel perspective on traditional clinical treatment research directions. We offer some constructive suggestions here, hoping that our ideas can contribute to a more comprehensive understanding of the mechanisms of SIGMAR1 in BC progression. We sincerely appreciate the time and effort you have invested in this research."	bladder